rs1325642993

Variant names:

• chr22-40251205-G-A
• rs1325642993
• NM_001162501.2:c.115+5G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-40251205-G-A
• chr22-40251205-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001162501.2(TNRC6B):​c.115+5G>A variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000000726 in 1,378,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: TNRC6B NM_001162501.2 splice_region, intron
• Scores: Splicing: ADA: 0.9440
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63
• Publications: 0 publications found

Genes affected

TNRC6B (HGNC:29190): (trinucleotide repeat containing adaptor 6B) Enables RNA binding activity. Involved in regulation of gene expression. Predicted to be located in cytosol. Predicted to be active in P-body and nucleoplasm. Implicated in subserous uterine fibroid and uterine fibroid. [provided by Alliance of Genome Resources, Apr 2022]

TNRC6B Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• global developmental delay with speech and behavioral abnormalities

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNRC6B	NM_001162501.2	c.115+5G>A		splice_region_variant, intron_variant	Intron 3 of 22	ENST00000454349.7	NP_001155973.1
TNRC6B	NM_015088.3	c.115+5G>A		splice_region_variant, intron_variant	Intron 3 of 20		NP_055903.2
TNRC6B	NM_001024843.2	c.223+5G>A		splice_region_variant, intron_variant	Intron 6 of 23		NP_001020014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNRC6B	ENST00000454349.7	c.115+5G>A		splice_region_variant, intron_variant	Intron 3 of 22	2	NM_001162501.2	ENSP00000401946.2
TNRC6B	ENST00000335727.13	c.115+5G>A		splice_region_variant, intron_variant	Intron 3 of 20	1		ENSP00000338371.8
TNRC6B	ENST00000402203.5	c.223+5G>A		splice_region_variant, intron_variant	Intron 6 of 23	1		ENSP00000384795.1
TNRC6B	ENST00000301923.13	c.223+5G>A		splice_region_variant, intron_variant	Intron 6 of 23	5		ENSP00000306759.9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 144580 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1378290 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 680334

African (AFR) AF: 0.00 AC: 0 AN: 30588

American (AMR) AF: 0.00 AC: 0 AN: 33836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24768

East Asian (EAS) AF: 0.00 AC: 0 AN: 35418

South Asian (SAS) AF: 0.00 AC: 0 AN: 77124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4958

European-Non Finnish (NFE) AF: 9.37e-7 AC: 1 AN: 1067270

Other (OTH) AF: 0.00 AC: 0 AN: 57080

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.82
PhyloP100		4.6

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.94
dbscSNV1_RF	Benign	0.57
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1325642993; hg19: chr22-40647209;